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To the Editor:-Anaphylactic reactions to thiopental occur in approximately 1 of every 30,000 patients. [1 ] Nonimmunologically mediated anaphylactoid reactions are based on direct histamine release and are believed to be more common; reported incidence for methohexital is 1 in 1,630. [2 ] However, immunologic documentation of the etiology of such reactions is not always clear. Hirshman et al. demonstrated in vitro thiopental-induced histamine release from the leukocytes of a patient who developed cardiovascular collapse and cutaneous flushing but had no evidence of an immunoglobulin E-mediated hypersensitivity with thiopental administration. [3 ] We present a patient in whom we documented what is probably a nonimmunologically mediated reaction to thiopental.

Our patient was a man aged 65 years (81 kg) scheduled for abdominal aneurysm repair. Standard monitors and an arterial catheter were placed before induction of general anesthesia. The preoperative blood pressure was 160/80 mmHg, and the heart rate was 65 beats/min. Induction was accomplished with 300 mg of thiopental. Immediately after thiopental administration, the heart rate increased to 140 beats/min, and the blood pressure decreased to 50/20 mmHg, and the face and upper chest became erythematous. Auscultation of the lungs disclosed no wheezing. Blood pressure did not increase with 300 micro gram of phenylephrine, but 150 micro gram of epinephrine corrected the hypotension, which lasted for about 10 min. The blood was drawn 10 min after the event for the histamine levels and 45 min after the event for other immunologic variables: histamine plasma concentration was 43 nmol/l (normal, 0–6 nmol/l); beta-tryptase serum concentration was less than 1 ng/ml (normal, less than 1 ng/ml); alpha-tryptase serum concentration was 7 ng/mL (normal, 1–10 ng/ml); C3complement, 79 mg/dl (normal, 76–199 mg/dl): C4complement, 22 mg/dl (normal, 16–64 mg/dl); and complement deficiency assay, 37 U (normal, 40–126 U). The allergologist performed skin testing with thiopental 30 days after surgery; the result was negative.

In vivo histamine is stored in mast-cells and basophils, while neutral protease, tryptase, is located in clinically significant concentrations only in the secretory granules of mast cells. [5 ] Therefore, increase in plasma histamine may reflect the degranulation of mast cells, basophils, or both types of cells, whereas increase in tryptase and histamine indicates specifically mast cells degranulation. [5 ] In our patient, the serum histamine concentration was elevated after thiopental without an elevated concentration of tryptase or abnormal complement concentrations. A similar clinical scenario was reported previously, although histamine levels were not measured. [6 ] It is possible that the cardiovascular collapse after thiopental administration resulted from histamine released from basophils, such as was described by Hirshman et al. [3 ] During systemic anaphylaxis, Beta-tryptase levels in blood begin to increase 15–30 min after antigenic challenge, peak at 30 min to 2 h, and decrease at the half-life of around 2 h. [7 ] In insect sting-induced anaphylaxis, tryptase levels correlate closely to the severity of the hypotension. [8 ] Consequently, undetectable serum Beta-tryptase after a profound hypotensive event indicates that the mast cells were not the primary cell type involved. At the same time, histamine plasma half-life is under 2 min, [7 ] and its elevated serum concentrations return to normal in 20–60 min after immunologic or nonimmunologic stimulation. [5 ] Therefore, an elevated serum tryptase can be used to confirm the diagnosis of mast cell-dependent anaphylaxis for several hours after the event, depending on the clinical severity and magnitude of mast cell degranulation.

We conclude that in our patient, thiopental administration caused hypotension mediated by histamine that most likely was released from basophils rather than mast cells.

Juraj Sprung, M.D., Ph.D.

Peter K. Schoenwald, M.D.

Department of General Anesthesiology, E-31; The Cleveland Clinic Foundation